CA125 outperforms NT-proBNP in the prediction of maximum aerobic capacity in heart failure with preserved ejection fraction and kidney dysfunction.

Background: Heart failure with preserved ejection fraction (HFpEF) often coexists with chronic kidney disease (CKD). Exercise intolerance is a major determinant of quality of life and morbidity in both scenarios. We aimed to evaluate the associations between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) with maximal aerobic capacity (peak VO2) in ambulatory HFpEF and whether these associations were influenced by kidney function. Methods: This single-centre study prospectively enrolled 133 patients with HFpEF who performed maximal cardiopulmonary exercise testing. Patients were stratified across estimated glomerular filtration rate (eGFR) categories (<60 ml/min/1.73 m2 versus ≥60 ml/min/1.73 m2). Results: The mean age of the sample was 73.2 ± 10.5 years and 56.4% were female. The median of peak VO2 was 11.0 ml/kg/min (interquartile range 9.0-13.0). A total of 67 (50.4%) patients had an eGFR <60 ml/min/1.73 m2. Those patients had higher levels of NT-proBNP and lower peak VO2, without differences in CA125. In the whole sample, NT-proBNP and CA125 were inversely correlated with peak VO2 (r = -0.43, P < .001 and r = -0.22, P = .010, respectively). After multivariate analysis, we found a differential association between NT-proBNP and peak VO2 across eGFR strata (P for interaction = .045). In patients with an eGFR ≥60 ml/min/1.73 m2, higher NT-proBNP identified patients with poorer maximal functional capacity. In individuals with eGFR <60 ml/min/1.73 m2, NT-proBNP was not significantly associated with peak VO2 [ß = 0.02 (95% confidence interval -0.19-0.23), P = .834]. Higher CA125 was linear and significantly associated with worse functional capacity without evidence of heterogeneity across eGFR strata (P for interaction = .620). Conclusions: In patients with stable HFpEF, NT-proBNP was not associated with maximal functional capacity when CKD was present. CA125 emerged as a useful biomarker for estimating effort intolerance in HFpEF irrespective of the presence of CKD.

Exercise training response according to baseline ferrokinetics in heart failure with preserved ejection fraction: A substudy of the TRAINING-HF trial.

BACKGROUND: Iron deficiency (ID) is associated with impaired functional capacity in patients with heart failure (HF), even in those with preserved ejection fraction (HFpEF). This study aimed to evaluate the effect of baseline ferrokinetics on peak oxygen consumption (peakVO2) improvement after a 12-week physical therapy programme in patients with stable HFpEF. METHODS: This study is a post-hoc sub-analysis of a randomized clinical trial in which 59 stable patients with HFpEF were randomized to receive a 12-week programme of inspiratory muscle training (IMT), functional electrical stimulation (FES), IMT + FES or usual care (UC) to evaluate change in peakVO2 (NCT02638961). Serum ferritin and transferrin saturation (TSAT) determinations were assessed at baseline. ID was defined as ferritin <100 ng/mL and/or TSAT <20% if ferritin was within 100-299 ng/mL. We used a linear mixed regression model to analyse between-treatment changes in peakVO2 across ferrokinetics status at 12 and 24 weeks. RESULTS: The mean age was 74 ± 9 years, and 36 (61%) had ID. The mean of peakVO2 was 9.9 ± 2.5 mL/kg/min. The median of ferritin and transferrin saturation (TSAT) was 91 (50-181) ng/mL and 23% (16-30), respectively. A total of 52 patients completed the trial (13 patients per arm). Compared with those patients on UC, patients allocated to any of the active arms showed less improvement in peak VO2 when they showed ID (P-value for interaction <0.001), lower values of ferritin (P-value for interaction <0.001), or TSAT (P-value for interaction <0.001). CONCLUSIONS: Ferrokinetics status plays an essential role in modifying the aerobic capacity response to physical therapies in patients with HFpEF. Further studies are required to confirm these findings.

Una mirada sociodemográfica a la incidencia de la COVID-19 en Cuba / A socio-demographic look at the incidence of COVID-19 in Cuba

Introducción: En Cuba el comportamiento de la epidemia de la COVID-19 ha sido analizado desde el enfoque de varias ciencias, con la guía de la Epidemiología, para frenar su expansión. Se requiere estudiar su comportamiento atendiendo al estado de la población para identificar sus diferenciales, lo cual puede ayudar en la adopción de medidas para su enfrentamiento. Objetivo: Evaluar la incidencia de la COVID-19 en Cuba a partir de indicadores sociodemográficos. Métodos: Se utilizaron los cálculos de las tasas de incidencia, mortalidad y la letalidad de la COVID-19 por grupos de edades y sexo a nivel de país y sus territorios. Se compararon estas tasas con indicadores demográficos seleccionados. Se utilizaron los datos aportados por diversos sitios oficiales del país en el periodo del 11 de marzo al 12 de junio de 2020. Resultados: La edad fue el principal diferencial de las tasas de mortalidad y la letalidad por COVID-19, con mayor frecuencia en los mayores de 60 años, fundamentalmente en hombres. No se evidenció ninguna variación proporcional entre dichas tasas y el grado de urbanización, la densidad poblacional y el grado de envejecimiento de la población. Conclusiones: Para disminuir el impacto de la COVID-19 en Cuba fueron decisivas las medidas adoptadas por el Gobierno, fundamentalmente las que estaban en función de los grupos más vulnerables. El estudio de los diferenciales de la COVID-19 desde la Demografía constituye un punto de partida para la búsqueda de factores de diversa naturaleza que influyen en su comportamiento(AU)

Introduction: In Cuba, the behavior of the COVID-19 epidemic has been analyzed from the approach of several sciences, with the guidance of Epidemiology, to stop its spread. It is necessary to study its behavior according to the state of the population to identify their differentials, which can help in the adoption of measures to confront them. Objective: Asses the incidence of COVID-19 in Cuba based on socio-demographic indicators. Methods: Calculations of COVID-19 incidence, mortality and lethality rates by age groups and sex were used at the country and territory levels. These rates were compared with selected demographic indicators. The data provided by various official sites of the country in the period from March 11 to June 12, 2020 were used. Results: Age was the main differential in mortality rates and lethality due to COVID-19, with greater frequency in those over 60 years of age, mainly in men. There was no evidence of any proportional variation between these rates and the degree of urbanization, population density and degree of population ageing. Conclusions: To reduce the impact of COVID-19 in Cuba, the measures adopted by the Government were decisive, mainly those that were based on the most vulnerable groups. The study of the differentials of COVID-19 from Demography constitutes a starting point for the search of different nature factors that influence its behavior(AU)

Short-term effects of dapagliflozin on maximal functional capacity in heart failure with reduced ejection fraction (DAPA-VO2 ): a randomized clinical trial.

AIMS: This study aimed to evaluate the effect of dapagliflozin on 1 and 3-month maximal functional capacity in patients with stable heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: In this multicentre, randomized, double-blind clinical trial, 90 stable patients with HFrEF were randomly assigned to receive either dapagliflozin (n = 45) or placebo (n = 45). The primary outcome was a change in peak oxygen consumption (peakVO2 ) at 1 and 3 months. Secondary endpoints were changes at 1 and 3 months in 6-min walk test (6MWT) distance, quality of life (Minnesota Living with Heart Failure Questionnaire [MLHFQ]), and echocardiographic parameters (diastolic function, left chamber volumes, and left ventricular ejection fraction). We used linear mixed regression analysis to compare endpoint changes. Estimates were adjusted for multiple comparisons. The mean age was 67.1 ± 10.7 years, 69 (76.7%) were men, 29 (32.2%) had type 2 diabetes, and 80 (88.9%) were in New York Heart Association class II. Baseline means of peakVO2 , 6MWT and MLHFQ were 13.2 ± 3.5 ml/kg/min, 363 ± 110 m, and 23.1 ± 16.2, respectively. The median (25th-75th percentile) of N-terminal pro-brain natriuretic peptide was 1221 pg/ml (889-2100). Most patients were on treatment with sacubitril/valsartan (88.9%), beta-blockers (91.1%), and mineralocorticoid receptor antagonists (74.4%). PeakVO2 significantly increased in patients on treatment with dapagliflozin (1 month: +Δ 1.09 ml/kg/min, 95% confidence interval [CI] 0.14-2.04; p = 0.021, and 3 months: +Δ 1.06 ml/kg/min, 95% CI 0.07-2.04; p = 0.032). Similar positive findings were found when evaluating changes from baseline. No significant differences were observed in secondary endpoints. CONCLUSIONS: Among patients with stable HFrEF, dapagliflozin resulted in a significant improvement in peakVO2 at 1 and 3 months. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04197635.

Effect of ß-Blocker Withdrawal on Functional Capacity in Heart Failure and Preserved Ejection Fraction.

BACKGROUND: Chronotropic incompetence has shown to be associated with a decrease in exercise capacity in heart failure with preserved ejection fraction (HFpEF), yet ß-blockers are commonly used in HFpEF despite the lack of robust evidence. OBJECTIVES: This study aimed to evaluate the effect of ß-blocker withdrawal on peak oxygen consumption (peak Vo2) in patients with HFpEF and chronotropic incompetence. METHODS: This is a multicenter, randomized, investigator-blinded, crossover clinical trial consisting of 2 treatment periods of 2 weeks separated by a washout period of 2 weeks. Patients with stable HFpEF, New York Heart Association functional classes II and III, previous treatment with ß-blockers, and chronotropic incompetence were first randomized to withdrawing from (arm A: n = 26) versus continuing (arm B: n = 26) ß-blocker treatment and were then crossed over to receive the opposite intervention. Changes in peak Vo2 and percentage of predicted peak Vo2 (peak Vo2%) measured at the end of the trial were the primary outcome measures. To account for the paired-data nature of this crossover trial, linear mixed regression analysis was used. RESULTS: The mean age was 72.6 ± 13.1 years, and most of the patients were women (59.6%) in New York Heart Association functional class II (66.7%). The mean peakVo2 and peak Vo2% were 12.4 ± 2.9 mL/kg/min, and 72.4 ± 17.8%, respectively. No significant baseline differences were found across treatment arms. Peak Vo2 and peak Vo2% increased significantly after ß-blocker withdrawal (14.3 vs 12.2 mL/kg/min [Δ +2.1 mL/kg/min]; P < 0.001 and 81.1 vs 69.4% [Δ +11.7%]; P < 0.001, respectively). CONCLUSIONS: ß-blocker withdrawal improved maximal functional capacity in patients with HFpEF and chronotropic incompetence. ß-blocker use in HFpEF deserves profound re-evaluation. (ß-blockers Withdrawal in Patients With HFpEF and Chronotropic Incompetence: Effect on Functional Capacity [PRESERVE-HR]; NCT03871803; 2017-005077-39).

Iron deficiency and short-term adverse events in patients with decompensated heart failure.

BACKGROUND: For patients with heart failure (HF), iron deficiency (ID) is a common therapeutic target. However, little is known about the utility of transferrin saturation (TSAT) or serum ferritin for risk stratification in decompensated HF (DHF) or the European Society of Cardiology's (ESC) current definition of ID (ferritin < 100 µg/L or TSAT < 20% if ferritin is 100-299 µg/L). We evaluated the association between these potential markers of ID and the risk of 30-day readmission for HF or death in patients with DHF. METHODS: We retrospectively included 1701 patients from a multicenter registry of DHF. Serum ferritin and TSAT were evaluated 24-72 h after hospital admission, and multivariable Cox regression was used to assess their association with the composite endpoint. RESULTS: Participants' median (quartiles) age was 76 (68-82) years, 43.8% were women, and 51.7% had a left ventricular ejection fraction > 50%. Medians for NT-proBNP, TSAT, and ferritin were 4067 pg/mL (1900-8764), 14.1% (9.0-20.3), and 103 ug/L (54-202), respectively. According to the current ESC definition, 1,246 (73.3%) patients had ID. By day 30, there were 177 (10.4%) events (95 deaths and 85 HF readmission). After multivariable adjustment, lower TSAT was associated with outcome (p = 0.009) but serum ferritin was not (HR 1.00; 95% confidence interval 0.99-1.00, p = 0.347). CONCLUSIONS: Lower TSAT, but not ferritin, was associated with a higher risk of short-term events in patients with DHF. Further research is needed to confirm these findings and the utility of serum ferritin as a marker of ID in DHF.

Heart rate response and functional capacity in patients with chronic heart failure with preserved ejection fraction.

AIMS: The mechanisms of exercise intolerance in heart failure with preserved ejection fraction (HFpEF) are not yet elucidated. Chronotropic incompetence has emerged as a potential mechanism. We aimed to evaluate whether heart rate (HR) response to exercise is associated to functional capacity in patients with symptomatic HFpEF. METHODS AND RESULTS: We prospectively studied 74 HFpEF patients [35.1% New York Heart Association Class III, 53% female, age (mean ± standard deviation) 72.5 ± 9.1 years, and 59.5% atrial fibrillation]. Functional performance was assessed by peak oxygen consumption (peak VO2 ). The mean (standard deviation) peak VO2 was 10 ± 2.8 mL/min/kg. The following chronotropic parameters were calculated: Delta-HR (HR at peak exercise - HR at rest), chronotropic index (CI) = (HR at peak exercise - resting HR)/[(220 - age) - resting HR], and CI according to the equation developed by Keteyian et al. (CIK) (HR at peak exercise - HR at rest)/[119 + (HR at rest/2) - (age/2) - 5 - HR at rest]. In a bivariate setting, peak VO2 was positively and significantly correlated with Delta-HR (r = 0.35, P = 0.003), CI (r = 0.27, P = 0.022), CIK (r = 0.28, P = 0.018), and borderline with HR at peak exercise (r = 0.22, P = 0.055). In a multivariable linear regression analysis that included clinical, analytical, echocardiographic, and functional capacity covariates, the chronotropic parameters were positively associated with peak VO2 . We found a linear relationship between Delta-HR and peak VO2 (ß coefficient of 0.03; 95% confidence interval: 0.004-0.05; P = 0.030); conversely, the association among CIs and peak VO2 was exponentially shaped. CONCLUSIONS: In patients with chronic HFpEF, the HR response to exercise was positively associated to patient's functional capacity.